Haemolytic anaemias Flashcards
Define anaemia
reduced haemoglobin level for the age and gender of the individual
What are classification of anaemias?
- on the basis of cause => blood loss, inadequate production, excessive destruction of blood cells
- on the basis of morphology=> normocytic, microcytic and macrocytic
what is haemolytic anaemia?
- anaemia due to shortened RBC survival (due to excessive breakdown of RBC)
What is normal RBC lifecycle?
- 2x10^11 RBC/ day in the bone marrow
- circulate for approx 120 days
- 300 miles travelled through microcirculation
- senescent RBC removed by RES
What happens in haemolysis life cycle?
- shortened RBC survival 30-80 days
- increase production By bone marrow to compensate
- this leads to increased young cells in circulation = reticulocytosis +/- nucleated RBC
- However RBC production unable to keep up with decreased RBC life span = decreased Hb
What are clinical findings?
- jaundice
- pallor
- fatigue
- splenomegaly
What are chronic clinical findings?
- gallstones - pigment
- leg ulcers
- folate deficiency (increased use to compensate for loss RBC)
What do lab investigation for HA show?
- peripheral blood film : polychromatophilia, nucleated RBC, thrombocytosis , neutrophilia with left shift;
- morphologic abnormalaties provide clue to underlying disorder, ie: spherocytes, sickle cell, target cells, schistocytes, acathocytes.
What are bone marrow findings in lab investigation for HA?
compensatory mechanism to haemolysis
- > erythroid hyperplasia of BM - with normoblastic rxn, reversal of M: E ration
- > reticulocytosis - variable
- mild (2-10%) hemoglobinopathies
- moderate to marked (10-60%) , seen in these conditions: IHAS, HS , G6PD def.
What are other findings in lab investigation of HA?
- increased unconjugated bilirubin
- increased LDH (Lactate dehydrogenase)
- Decreased serum haptoglobin protein that binds free Hb
- incresed urobilinogen
- increased urinary hemosiderin
What are classifications of haemolytic anaemia?
- inheritance
- hereditary
(hereditary spherocytosis)
-acquired ( IHA) - site of RBC destruction
- intravascular (hemolytic transfusion Rxn)
- extravascular (autoimmune haemolysis) - Origin of RBC damage
- intrinsic aka intracorpuscular (G6PD deficiency)
- extrinsic aka extracorpuscular (infection)
What are the site of RBC destruction?
1. extravascular (normal) unconjugated bilirubin ->liver ->gut -> kidney 2. intravascular (abnormal) Hb -> kidney
What 2 conditions does defect in the membrane protein of RBC lead to?
- heriditary spherocytosis
- autosomal dominant
- caused by defects in vertical interactions - hereditary elliptocytosis
- defects in the horizontal interactions
- loss of interaction between a and b spectrin.
What are clinical features of heriditary spherocytosis?
- neonatal jundice
- asymptomatic to severe haemolysis
- splenomegaly
- pigment gallstones
- reduced eosin-50 maleimide (EMA) binding -binds to band 3
- positive family history
- negative direct antibody test
What is the role of hexose monophasphate shunt (HMP)?
- generate NADPH and reduced Glutathione
- protects the cell from oxidative stress
What is the effects of deficiency of HMP?
oxidative stress
- oxidation of Hb by oxidant radicals resulting in denatured Hb aggregates and forms heinz bodies
- oxidised membrane = proteins reduced RBC deformability
What is the function of pyruvate kinase pathway?
- glycolytic pathway = generates energy in ATP
-to maintain red cell shape and deformability
-to regulate intracellular cation conc. via cation pump(Na/K pump)
=>defects in this pathway leads to defects in the RBC shape and deform ability
Deformability important to allow RBC to squeeze through vessels
What are 2 globin disorders?
- Thalassaemia - quantitative
- defect in the rate of synthesis of alpha - beta globin chain (structurally normal) - variant haemoglobins - qualitative
- production of structurally abnormal globin chain
What are thalassaemias?
- imbalanced alpha and beta chain production
- excess unpaired globin chains are unstable
- heterogenous disorder
- ineffective erythropoiesis
What are thalassaemias clinically divided into?
- hydrop foetalis (alpha)
- beta thalassaemia
- thalassaemia intermedia
- thalassaemia minor
Alpha thalassaemia
Hb barts hydrops syndrome
- deletion of all 4 globin gene
- incompatible with life
HbH disease
-deletion of 3/4 alpha globin genes
-common in SE asia
=>clinical features:
-moderate chronic HA, splenomegaly, hepatomegaly
-hypochromic microlytic, poikilocytosis, poly chromasia, target cells.
-electropherosis diagnostic
Trait minor:
- normal or mild HA
- MCV and MCH low
Beta thalassaemia major
clinical features:
- severe anaemia
- progressive hepatosplenomegaly
- bone marrow expansion - facial bone abnormalities
- mild jaundice
- iron overload
- intermittent infections
peripheral blood
- microcytic hypochromic with decreased MCV, MCH, MCHC
- anispoikilocytosis, target cells, nucleated RBC, tear drop cells
- reticulocytes >2%
Thalassemia intermedia
disorder with clinical manifestation between major and minor
- transfusion independent
- diverse clinical phenotype
- varying symptoms
- increased bilirubin level
- diagnosed -largely clinical
Thalassemia minor
- asymptomatic
- often confused with Fe deficiency
- a- thal trait often by exclusion
- HbA2 increased in beta thal trait
What is sickle cell disease?
-refers to all disease as a result of inherited HbS
What causes SCD?
=>HbS is caused by a single nucleotide substitution.
- HbSS = sickle cell anemia (homozygous)
- HbAS = Sickle cell trait (heterozygous)
point mutation in beta globin gene glutamic acid -> valine at position 6.
insoluble Hb tetramer when deoxygenated -> polymerisation = sickle cell shape
Clinical features of SCD
- painful crises
- aplastic crises
- infections
- acute sickling =chest syndrome, splenic detach, stroke
- chronic sickling effect = renal failure, avascular necrosis
Lab feature of SCD
- anaemia : 60 to 90 Hb
- reticulocytosis
- increased NRBC
- raised bilirubin
- low creatine
How do you confirm sickle cell diagnosis?
=> soluability test
- exposure blood to reducing agent
- HbS precipitated
- positive in trait and disease
features of hemolysis
- jaundice
- pallor
- splenomegaly
- reticulocytosis
- unconjugated hyperbillirubinaemia
- raised LDH
Hemolytic anemia can be classified into intrinsic and extrinsic, what does intrinsic anemia include?
- Membrane defects
- Enzyme defects
- Hemoglobin defects
What two categories can extrinsic HA be divided into?
- Immune mediated
- autoimmune
- alloimmune - Non immune
- RBC fragmentation
- mechanical trauma
- drugs and chemicals
